Atypical fibroxanthoma-like melanoma: A rare subtype of high-cumulative sun damage melanoma with partial dedifferentiation and an aggressive molecular profile

Background: We report a rare case of atypical fibroxanthoma (AFX)-like melanoma on the scalp of a 75- year-old man. This case illustrates the phenomenon of melanoma dedifferentiation, resulting in an AFXlike appearance.

Case Presentation: A biopsy of an erythematous, tender nodule on the left posterior parietal scalp revealed an ulcerated nodular lesion composed of epithelioid and spindle cells with pleomorphic nuclei arranged in a fascicular pattern. The tumor's architectural and cytologic features, including the presence of an epidermal collarette, marked anisonucleosis, and numerous atypical mitoses, closely resembled those of AFX. Immunohistochemical analysis demonstrated SOX10 positivity and negativity for other melanocytic markers. Molecular profiling confirmed the diagnosis of melanoma and identified mutations in the TERT promoter, NRAS, NF1, PBRM1, FAT1, and ATM genes. The tumor was categorized as Class 2B by the DecisionDx-Melanoma test, indicating a high risk of recurrence and metastasis. Sentinel lymph node excision revealed metastatic melanoma in 2 of the 5 examined nodes, further supporting the aggressive biological nature of this neoplasm.

Discussion: Various molecular mechanisms potentially underly this transformation, with mutations in NF1, PBRM1, and FAT1 likely contributing to the tumor's atypical morphology and loss of melanocytic markers. The high tumor mutational burden and aggressive molecular profile align with the reported poor prognosis of dedifferentiated melanomas. Recognizing this rare variant is critical for accurate diagnosis, effective patient management, and prognosis assessment.